Imaging Biomarkers for the Diagnosis and Prognosis of Neurodegenerative Diseases. The Example of Amyotrophic Lateral Sclerosis

The term amyotrophic lateral sclerosis (ALS) comprises a heterogeneous group of fatal neurodegenerative disorders of largely unknown etiology characterized by the upper motor neurons (UMN) and/or lower motor neurons (LMN) degeneration. The development of brain imaging biomarkers is essential to advance in the diagnosis, stratification and monitoring of ALS, both in the clinical practice and clinical trials. In this review, the characteristics of an optimal imaging biomarker and common pitfalls in biomarkers evaluation will be discussed. Moreover, the development and application of the most promising brain magnetic resonance (MR) imaging biomarkers will be reviewed. Finally, the integration of both qualitative and quantitative multimodal brain MR biomarkers in a structured report will be proposed as a support tool for ALS diagnosis and stratification

Carbono orgânico nos solos do norte de Espanha (Galiza, Astúrias, Cantabria e País Basco)

The soil organic carbon content was analyzed in more than 7 000 soil samples under different land uses, climates and lithologies from northern Spain (Galicia, Asturias, Cantábria y País Vasco). GIS maps (1:50 000) were made of the % SOC and SOC stocks. The % SOC varies according to land use (higher in forest and scrub soils and lower in agricultural soils) and climate, and there is a highly significant correlation between SOC content and mean annual precipitation. There are significant differences between the soils of Galicia/Western Asturias (GAw) and those of the rest of the study area (Central and Eastern Asturias, Cantabria and País Vasco) (AceCV), although these are neighbouring regions. In forest and/or scrub soils with a udic soil moisture regime, in GAw, the SOC is usually > 7% and the average stocks 260 t ha -1 (0-30 cm), and >340 t ha-1 (0-50 cm) in soils with thick organic matter rich horizons (> 40 cm); these values greatly exceed the average contents observed in forest soils from temperate zones. Under similar conditions of vegetation and climate in soils of AceCV the SOC average is 3% and the mean stocks 90-100 t ha-1 (0-30 cm). The andic character of acid forest soils in GAw and the formation of C-Al,Fe complexes are pointed out as the SOC stabilization mechanism, in contrast to the neutral and calcareous soils that predominate in AceCV, where the main species of OC are easily biodegradable.Se analiza el contenido de carbono orgánico (CO) en más de 7.000 muestras de suelos del norte de España (Galicia, Asturias, Cantábria y País Vasco) bajo diferentes tipos de ocupación, condiciones climáticas y litología, y se elaboran mapas SIG (1:50 000) del porcentaje y stock de carbono en los suelos. El porcentaje de CO varía de acuerdo al uso del suelo (mayor en suelos forestales y con matorral, y menor en suelos de cultivo) y al clima, reconociéndose una correlación altamente significativa entre el porcentaje de CO y la precipitación media anual. En cualquier caso, aún tratándose de regiones próximas, se establecen diferencias importantes entre los suelos de Galicia-oeste de Asturias (G/Ao ) y los del resto del área de estudio (Asturias central y oriental, Cantabria y País Vasco) (AceCV). En suelos forestales y/o con matorral y régimen de humedad údico, en G/Ao , el porcentaje de CO es habitualmente > 7% y el stock medio 260 tC ha-1 (0-30 cm) y puede ser > 340 tC ha-1 (0-50 cm), teniendo en cuenta la abundancia de suelos con rasgos cumúlicos y horizontes humíferos con > 40 cm de espesor; los valores obtenidos superan ampliamente los contenidos medios señalados por diferentes autores para suelos forestales de áreas templadas. En similares condiciones de vegetación y clima, el contenido medio de CO en suelos de (AceCV) es de 3% y el stock medio 90-100 tC ha-1 (0-30 cm). El carácter ándico de los suelos forestales ácidos de G/Ao, y la formación de complejos C-Al,Fe se señala como mecanismo de estabilización del CO, en contraste con los suelos neutros y calcáreos que predominan en AceCV, en los que la especie principal es el CO fácilmente biodegradable.Analisou-se o teor de carbono orgânico en mais de 7.000 amostras de solo do norte de Espanha (Galiza, Astúrias, Cantábria e País Basco), sob diferentes usos, condições climáticas e litologias, e procedeu-se ao mapeamento SIG (1:50 000) da percentagem e stock de carbono nos solos. A percentagem de CO varia de acordo com o uso do solo (maior em solos de floresta e mata e menor em solos agrícolas) e condições climáticas, observando-se uma correlação altamente significativa entre a percentagem de CO e a precipitação média anual. Em qualquer caso, mesmo para regiões vizinhas, registam-se diferenças significativas entre os solos da Galiza-oeste e das Astúrias (G/Ao) e o resto da área em estudo (Astúrias central e oriental, Cantabria e País Basco) (AceCV). Em solos de floresta e/ou de mata e regime de humidade údico, em G/Ao, a percentagem de CO é geralmente > 7% e o stock médio 260 t C ha-1(0-30 cm), e > 340 t C ha-1 (0-50 cm) em solos com espessos horizontes ricos em matéria orgânica (> 40 cm); estes valores excedem largamente os teores médios observados em solos florestais de zonas temperadas. Em condições semelhantes de vegetação e clima, em solos de AceCV, o teor médio de CO é de 3% e o stock médio de 90-100 t C ha-1 (0-30 cm). O carácter andico dos solos florestais ácidos da Galiza, e a formação do complexos C-Al,Fe são apontados como o mecanismo de estabilização do CO, em contraste com os solos neutros e calcários prevalecentes em AceCV, onde a espécie predominante é o CO facilmente biodegradável.This study was supported by the Spanish Ministry of Science and Innovation, National Plan I+D, through project CGL2009-13857S

Soil organic carbon in peninsular Spain: Influence of environmental factors and spatial distribution

Soil organic carbon (SOC) stocks and their geographical distribution in peninsular Spain were estimated from a georeferenced database consisting of 12,724 surface samples (0–30 cm) and 3607 subsurface samples (30–50 cm), covering different climate, land use, elevation, parent material, soil type and soil pH. SOC density showed a high heterogeneity, with the lowest values in arid regions, where the average in topsoil ranged between 20 and 60 t C ha−1, under woody crops and forest respectively. Carbon stocks gradually increases as precipitation increases, and its variability is also dependent of other factors, fundamentally the presence/absence of active lime or active Al. In semi-arid zones, calcaric soils (pH ≈ 8.3) have higher contents of SOC than neutral to weakly acidic soils from siliceous materials. However, in humid regions, calcareous materials have undergo total or partial decarbonatation in the upper layer (pH < 4.0–7.5) and SOC stocks are markedly lower than in other materials. In forest soils it seems that a steady state (around 100–120 t C ha−1) (0–30 cm) has been reached in a wide range of precipitation, between 900 and 1700 mm; most of this carbon (about 80%) is labile-C. Soils from granitic rocks are acidic (pH 4.5–5.5) (Al buffering) and the mean SOC stock in the indicated precipitation range is between 170 and 200 t ha−1 (it is estimated that approximately 60% is stabilized as metal-C or mineral-C complexes). The highest values (190–240 t ha−1) are recorded in acidic soils derived from mafic rocks, which in these regions usually develop andic properties (around 73% is involved in stable metal-C or mineral C complexes). Finally, the SOC stored in neutral soils from serpentinized ultramafic rocks (without excess Ca or Al) is similar to that of the decarbonated soils derived from calcareous materials. In all regions, forest soils are a much more important SOC sink than live forest biomass (2–4 times higher in the upper 30 cm and 3–6 times greater in the upper 50 cm). Random Forest regression was used as modeling tool and digital mapping. Mean annual precipitation was estimated to be the most important predictor variable, followed by land use, lithology/soil type and soil pH. Model performance was calibrated by the internal RF validation and through cross-validation, and the results were similar. In topsoil, the mean error, root mean square error and R2 were −0.007% C, 1.48% C and 0.61, respectively. In the subsurface layer these indices were −0.020, 1.07 and 0.37, respectively. SOC stock for peninsular Spain was estimated at 3.33 Pg in the upper (0–30 cm) layer, and 0.85 Pg in the subsurface (30–50 cm) layer. Total SOC stock for 0–50 cm was 4.19 Pg, with a 95% confidence interval ranging between 3.33 and 5.03 PgThis work was supported by the Ministry of Science and Innovation, Spain (CGL2009, 13857: 2010-2014); and the Consellería de Educación-Xunta de Galicia, Spain (2014-GRC GI-124, 2014-2017)S

Assessment of levels of anxiety and fear of Covid-19 in a population of pregnant women in Spain

Objective: The aim of the study was to assess the levels of fear and anxiety in the particularly vulnerable population group of women during pregnancy.Methods: Cross-sectional study between March 2022 and July 2022 involving 978 pregnant women aged 16 to 50 years. It was carried out based on the scale for the assessment of fear and anxiety in pregnant women (AMICO_Pregnant) and the collection of sociodemographic data. Normality analysis was performed prior to univariate and bivariate statistical analysis.Results: The sample was composed of a total of 978 pregnant women. The mean of the AMICO_Pregnant scale was intermediate (5.04 points; SD=2.36). The bivariate analysis showed a statistically significant relationship between the AMICO_Pregnant scale and the following variables: vaccination schedule status, contact with the disease, weeks of gestation, altered delivery or birth plan.Conclusion: Women with pregnancies closer to term, with no contact with the disease, without a complete vaccination schedule, or who had undergone changes in their delivery or birth plans, showed higher levels of fear and anxiety.info:eu-repo/semantics/publishedVersio

Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population

Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, >= 27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with >= 27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with = 27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype

Characterizing the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations

[EN] Background Mutations in the metalloendopeptidase (MME) gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in MME were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in MME. Methods We screened 197 index cases with a hereditary neuropathy of the CMT type or distal hereditary motor neuropathy (dHMN) and 10 probands with familial amyotrophic lateral sclerosis (fALS) using a custom panel of 119 genes. In addition to the index case subjects, we also studied other clinically and/or genetically affected and unaffected family members. Results We found 17 variants in MME in a total of 20 index cases, with biallelic MME mutations detected in 13 cases from nine families (three in homozygosis and six in compound heterozygosis) and heterozygous variants found in 11 families. All patients with biallelic variants had a similar phenotype, consistent with late-onset axonal neuropathy. Conversely, the phenotype of patients carrying heterozygous mutations was highly variable [CMT type 1 (CMT1), CMT2, dHMN and fALS] and mutations did not segregate with the disease. Conclusion MME mutations that segregate in an autosomal recessive pattern are associated with a late-onset CMT2 phenotype, yet we could not demonstrate that MME variants in heterozygosis cause neuropathy. Our data highlight the importance of establishing an accurate genetic diagnosis in patients carrying MME mutations, especially with a view to genetic counselling.The authors thank the patients and healthy relatives for having participated in this project. We are grateful to the Eurobiobank CIBERER and the Biobank La Fe for their participation in the collection and processing of patient samples. We also thank the technicians at the Department of Genomics and Translational Genetics (CIPF) who participated in the quality control and processing of DNA samples (Virginia Rejas and Laura Ramírez), and the Bachelor¿s thesis student Andrea Ballester who helped with some clinical data collection. This project was funded by the Instituto de Salud Carlos III (ISCIII), FEDER (Grants no. PI12/00946 and PI16/00403 to TS, PI15/00187 to CE). MF holds a grant funded by the IIS La Fe (Grant no. 2015/0085). AS-M holds a grant funded by the Fundació Per Amor a l'Art (FPAA). JFV-C holds a ' Rio Hortega' contract funded by the ISCIII.Lupo, V.; Frasquet, M.; Sánchez-Monteagudo, A.; Pelayo-Negro, A.; García-Sobrino, T.; Sedano, MJ.; Pardo, J.... (2018). Characterizing the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations. Journal of Medical Genetics. 55(12):814-823. https://doi.org/10.1136/jmedgenet-2018-105650814823551

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p=0.003; 52 (34.4%) vs 35 (23.2%), p=0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.S

From the sierra to the lowlands: new data on the settlement of the Barbanza Peninsula from Prehistoric to Medieval times

Procédese á revisión dos traballos de prospección previa na serra do Barbanza e ampliados aos montes de Macenda e Bealo na procura de asentamentos gandeiros/pastorís, no curso deses traballos localizáronse ademáis un interesante xacemento de cronoloxía calcolítca e un castro inédito. Asemade, dáse conta dos resultados das intervencións en dous xacementos, un de carácter gandeiro que presenta un palimpsesto estrutural e cronolóxico (Río Barbanza), e outro relacionado con sistemas de control territorial (Outeiro da Torre).We review the survey works carried through in the district of Barbanza, now extended to the parishes of Macenda and Bealo in search of livestock / pastoral settlements. In the course of these explorations a Copper Age site was discovered and, nearby, a previously unknown hillfort. An account is given of the results of the digging in two sites; one related to husbandry tasks, that presents a structural and chronological palimpsest (Rio Barbanza); and another more, related to territorial control systems (Outeiro da Torre)

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2